Self-injection device

ABSTRACT

A device ( 100 ) for delivering a medicament into a patient&#39;s body by injection into or through the patient&#39;s skin, including: a main body having a bottom enclosure ( 104 ) that has a top surface including a button guide latch ( 268 ); a reservoir ( 160 ) disposed within the main body for containing the medicament; an injection needle ( 152 ) for penetrating the skin of the patient, the needle ( 152 ) having a lumen and communicating with the reservoir ( 160 ) when the device ( 100 ) is activated; a pressurizing system ( 140, 144 ) for pressurizing the reservoir ( 160 ) when the device ( 100 ) is activated; and an activator button ( 128 ) movably disposed on the main body and movable from a pre-activated position to an activated position. The activator button ( 128 ) includes an activation arm ( 228 ). When the activator button ( 128 ) moves from the pre-activated position to the activated position, an end of the activation arm ( 228 ) engages with the button guide latch ( 268 ) and prevents return movement of the activator button ( 128 ).

RELATED APPLICATIONS

This application is a division of U.S. patent application Ser. No.13/516,142, filed on Aug. 13, 2012, which is the U.S. national stage ofInternational Application No. PCT/US09/06575, filed on Dec. 16, 2009.Each of these applications is hereby incorporated by reference in itsentirety.

FIELD OF THE INVENTION

The present invention relates generally to a substance delivery devicehaving improved patient convenience and ease of use, and improvedactivation and safety mechanisms. The present invention also relatesgenerally to a patch-like, self-contained substance infusion orself-injection device that can be used to deliver a variety ofsubstances or medications to a patient. More specifically, the presentinvention relates to a patch-like infusion or self-injection device thathas an activation lock.

BACKGROUND OF THE INVENTION

A large number of people, such as those suffering from conditions suchas diabetes, use some form of infusion therapy, such as daily insulininfusions, to maintain close control of their glucose levels. Currently,in the insulin infusion treatment example, there are two principal modesof daily insulin therapy. The first mode includes syringes and insulinpens. These devices are simple to use and are relatively low in cost,but they require a needle stick at each injection typically three tofour times per day. The second mode includes infusion pump therapy,which entails the purchase of an expensive pump that lasts for aboutthree years. The high cost (roughly 8 to 10 times the daily cost ofsyringe therapy) and limited lifetime of the pump are high barriers tothis type of therapy. Insulin pumps also represent relatively oldtechnology and are cumbersome to use. From a lifestyle standpoint,moreover, the tubing (known as the “infusion set”) that links the pumpwith the delivery site on the patient's abdomen is very inconvenient andthe pumps are relatively heavy, making carrying the pump a burden. Froma patient perspective, however, the overwhelming majority of patientswho have used pumps prefer to remain with pumps for the rest of theirlives. This is because infusion pumps, although more complex thansyringes and pens, offer the advantages of continuous infusion ofinsulin, precision dosing and programmable delivery schedules. Thisresults in closer glucose control and an improved feeling of wellness.

Interest in better therapy is on the rise, accounting for the observedgrowth in pump therapy and increased number of daily injections. In thisand similar infusion examples, what is needed to fully meet thisincreased interest is a form of insulin delivery or infusion thatcombines the best features of daily injection therapy (low cost and easeof use) with those of the insulin pump (continuous infusion andprecision dosing) and that also avoids the disadvantages of each.

Several attempts have been made to provide ambulatory or “wearable” druginfusion devices that are low in cost and convenient to use. Some ofthese devices are intended to be partially or entirely disposable. Intheory, devices of this type can provide many of the advantages of aninfusion pump without the attendant cost and inconvenience.Unfortunately, however, many of these devices suffer from disadvantagesincluding patient discomfort (due to the gauge and/or length ofinjection needle used), compatibility and interaction between thesubstance being delivered and the materials used in the construction ofthe infusion device, and possible malfunctioning if not properlyactivated by the patient (for example, “wet” injections resulting frompremature activation of the device). Difficulties in manufacturing andin controlling needle penetration depth have also been encountered,particularly when short and/or fine-gauge injection needles are used.The possibility of needle-stick injuries to those who come into contactwith the used device has also been problematic.

Accordingly, a need exists for an alternative to current infusiondevices, such as infusion pumps for insulin, that further providessimplicity in manufacture and use improvements for insulin andnon-insulin applications.

SUMMARY OF THE INVENTION

An aspect of the present invention is to provide a patch-like infusionor self-injection device that can be conveniently worn against the skinwhile providing infusion of a desired substance, and providing minimaldiscomfort by using one or more microneedles. An additional aspect ofthe present invention is to provide such an infusion or self-injectiondevice in which a patient can quickly and easily determine whether thedevice has been activated.

The foregoing and/or other aspects of the present invention are achievedby providing a device for delivering a medicament into a patient's bodyby injection into or through the patient's skin. The device includes amain body having a bottom enclosure that has a top surface including abutton guide latch, a reservoir disposed within the main body forcontaining the medicament, and an injection needle for penetrating theskin of the patient. The needle has a lumen and communicates with thereservoir when the device is activated. The device also includes apressurizing system for pressurizing the reservoir when the device isactivated, and an activator button movably disposed on the main body andmovable from a pre-activated position to an activated position. Theactivator button includes an activation arm. When the activator buttonmoves from the pre-activated position to the activated position, an endof the activation arm engages with the button guide latch and preventsreturn movement of the activator button.

The foregoing and/or other aspects of the present invention are alsoachieved by providing a device for delivering a medicament into the bodyof a patient by injection into or through the skin of a patient, thatincludes a main body including a top enclosure and a bottom enclosure,the bottom enclosure having a top surface including a button guide latchhaving a guide surface and a retaining surface. The device also includesa reservoir disposed within the main body forming a chamber forcontaining the medicament, and an injection needle for penetrating theskin of the patient. The needle has a lumen and communicates with thereservoir when the device is activated. The device further includes apressurizing system for pressurizing the reservoir when the device isactivated, and an activator button movably disposed on the main body andmovable from a pre-activated position to an activated position, theactivator button including an activation arm with a cutout and a lockingportion having a bearing surface and a locking surface. When theactivator button moves from the pre-activated position to the activatedposition, the bearing surface contacts and slides along the guidesurface of the button guide latch, elastically deforming at least one ofthe activation arm and the guide surface until an end of the guidesurface is reached. Additionally, when the activator button moves fromthe pre-activated position to the activated position, the cutout permitsthe activation arm to pass over the end of the guide surface, engagingthe locking surface with the retaining surface of the button guide latchto prevent return movement of the activator button.

The foregoing and/or other aspects of the present invention are alsoachieved by providing a device for delivering a medicament into apatient's body by injection into or through the patient's skin, whichincludes a main body having a top enclosure and a bottom enclosure, thebottom enclosure having a top surface including a button guide latch.The device also includes a reservoir disposed within the main body forcontaining the medicament, and an injection needle for penetrating theskin of the patient. The needle has a lumen and selectively communicateswith the reservoir. The device further includes a pressurizing systemfor pressurizing the reservoir, and an activator button movably disposedon the main body and movable from a pre-activated position to anactivated position. The activator button includes an activation arm.When the activator button moves from the pre-activated position to theactivated position, an end of the activation arm engages with the buttonguide latch and prevents return movement of the activator button.Movement of the activator button from the pre-activated position to theactivated position performs at least one function selected from thegroup of driving the injection needle to penetrate the patient's skin,pressurizing the reservoir, and establishing fluid communication betweenthe reservoir and the patient needle.

Additional and/or other aspects and advantages of the present inventionwill be set forth in part in the description that follows and, in part,will be apparent from the description, or may be learned by practice ofthe invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and/or other aspects and advantages of embodiments of theinvention will be more readily appreciated from the following detaileddescription, taken in conjunction with the accompanying drawings, ofwhich:

FIG. 1 illustrates a perspective view of an embodiment of a patch-likeinfusion or self-injection device in a pre-activated state prior toactivation;

FIG. 2 illustrates a partially exploded view of the infusion device ofFIG. 1 in the pre-activated state;

FIG. 3 illustrates a partially exploded view of the infusion device ofFIG. 1 in the pre-activated state with an activator button rotated awayto reveal more detail;

FIG. 4 illustrates a more fully exploded view of the infusion device ofFIG. 1 in the pre-activated state;

FIG. 5 illustrates a cross-sectional view of the infusion device of FIG.1 in the pre-activated state;

FIG. 6 illustrates a cross-sectional view of the infusion device of FIG.1 in the pre-activated state with the activator button rotated away;

FIG. 7 illustrates a partially exploded view of the infusion device ofFIG. 1 during installation of a safety mechanism;

FIG. 8 illustrates a partially exploded view of the infusion device ofFIG. 1 subsequent to activation;

FIG. 9 illustrates a more fully exploded view of the infusion device ofFIG. 1 subsequent to activation;

FIG. 10 illustrates a cross-sectional view of the infusion device ofFIG. 1 subsequent to activation;

FIGS. 11A and 11B illustrate embodiments of an activation arm of anactivator button of the infusion device of FIG. 1;

FIG. 12 illustrates a button guide latch of the infusion device of FIG.1;

FIGS. 13A and 13B respectively illustrate interaction between theactivation arm and the button guide latch prior to and subsequent toactivation of the infusion device of FIG. 1;

FIGS. 14A and 14B respectively illustrate another embodiment of thebutton guide latch prior to and subsequent to activation of the infusiondevice of FIG. 1;

FIG. 15 illustrates a partially exploded view of the infusion device ofFIG. 1 subsequent to deployment of the safety mechanism;

FIG. 16 illustrates a cross-sectional view of the infusion device ofFIG. 1 subsequent to deployment of the safety mechanism;

FIG. 17 illustrates a bottom surface of the safety mechanism;

FIG. 18 further illustrates the structure of the safety mechanism;

FIGS. 19A-19D illustrate an end-of-dose indicator and the operationthereof in the infusion device of FIG. 1; and

FIG. 20 illustrates an embodiment of an infusion device with aninjection port.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Reference will now be made in detail to embodiments of the presentinvention, examples of which are illustrated in the accompanyingdrawings, wherein like reference numerals refer to the like elementsthroughout. The embodiments described exemplify the present invention byreferring to the drawings.

The embodiments of the present invention described below can be used asa convenient, patch-like infusion or self-injection device 100 todeliver a pre-measured dose of a substance, such as a liquid drug ormedication, to a patient over a period of time or all at once. Thedevice is preferably provided to the end user in a pre-filled condition,that is, with the drug or medication already contained in the devicereservoir. Though the patch-like infusion or self-injection device 100(shown, for example, in FIG. 1) described herein can be employed by apatient and/or a caregiver, for convenience, a user of the device ishereinafter referred to as a “patient.” Additionally, for convenience,terms such as “vertical” and “horizontal” and “top” and “bottom” areemployed to represent relative directions with respect to an infusiondevice 100 disposed on a horizontal surface. It will be understood,however, that the infusion device 100 is not limited to such anorientation, and that the infusion device 100 may be employed in anyorientation. Further, the alternative use of the terms “infusion device”and “self-injection device” to describe devices embodying the presentinvention is not intended in a limiting sense. Infusion devices that donot have a self-injection capability are within the scope of the presentinvention, as are self-injection devices that do not carry outcontinuous infusion. For convenience, but not by way of limitation, theterm “infusion device” is used in the description that follows.

The patch-like infusion device 100 of FIG. 1 is self-contained and isattached to the skin surface of the patient by adhesive disposed on abottom surface of the infusion device 100 (as will be described ingreater detail below). Once properly positioned and activated by thepatient, the pressure of a released spring on a flexible reservoirwithin the device can be used to empty the contents of the reservoirthrough one or more patient needles (for example, microneedles) via aneedle manifold. The substance within the reservoir is then deliveredthrough the skin of the patient by the microneedles, which are driveninto the skin. It will be understood that other embodiments are possiblein which the spring is replaced with a different type of stored energydevice, which may be mechanical, electrical and/or chemical in nature.

As will be appreciated by one skilled in the art, there are numerousways of constructing and using the patch-like infusion device 100disclosed herein. Although reference will be made to the embodimentsdepicted in the drawings and the following descriptions, the embodimentsdisclosed herein are not meant to be exhaustive of the variousalternative designs and embodiments that are encompassed by thedisclosed invention. In each disclosed embodiment, the device isreferred to as an infusion device, but the device may also injectsubstances at a much faster (bolus) rate than is commonly accomplishedby typical infusion devices. For example, the contents can be deliveredin a period as short as several seconds or as long as several days.

In an embodiment of the device, a push-button design of the patch-likeinfusion device 100 is shown wherein the activation and energizing ofthe device is accomplished in a single multi-function/step process. FIG.1 illustrates an assembled embodiment of the infusion device 100 in apre-activated state. FIGS. 2-6 illustrate partially exploded andcross-sectional views of the infusion device 100 in the pre-activatedstate, FIG. 7 illustrates a partially exploded view of the infusiondevice 100 during installation of a safety mechanism, FIGS. 8-10illustrate exploded and cross-sectional views of the infusion device 100subsequent to activation, and FIGS. 15 and 16 illustrate exploded andcross-sectional views of the infusion device 100 subsequent todeployment of the safety mechanism. The infusion device 100 isconfigured to operate between the pre-activated state (shown, forexample, in FIGS. 1, 2, and 5), an activated or fired state (shown, forexample, in FIGS. 8-10), and a retracted or safe state (shown, forexample, in FIGS. 15 and 16).

As shown in FIG. 1, an embodiment of the patch-like infusion device 100includes a bottom enclosure 104, a safety mechanism 108, a flexibleneedle cover 112, a top enclosure 116, a reservoir subassembly 120, anend-of-dose indicator (EDI) 124, and an activator button 128, whichincludes a patient interface surface 132. Additionally, as shown inFIGS. 2-6, the infusion device 100 also includes a rotor or activationring 136, a pressurization spring 140, a dome-like metal plunger 144,and a drive spring 148.

The flexible needle cover 112 provides patient and device safety byprotecting at least one needle 152 (described in greater detail below)and providing a sterile barrier. The needle cover 112, protects theneedle 152 during device manufacture, protects the patient prior to use,and provides a sterility barrier at any point prior to removal.According to one embodiment, the needle cover 112 is attached via apress fit with a needle manifold in which the at least one needle 152 isdisposed. Additionally, according to one embodiment, a needle opening156 (described in greater detail below) of the safety mechanism 108 isshaped to closely correspond to a perimeter of the needle cover 112.

As shown, for example, in FIGS. 2-6, the reservoir subassembly 120includes a reservoir 160, a reservoir dome seal 164, a valve 168, atleast one needle 152, and at least one channel arm 172 (see, forexample, FIG. 8) disposed between the valve 168 and the needle 152 andcreating a flow path therebetween. The reservoir 160 includes a dome176. Additionally, the reservoir subassembly 120 includes the removableneedle cover 112 to selectively cover the at least one needle 152.According to one embodiment, the reservoir subassembly 120 also includesa reservoir arm seal 180, covering the channel arm 172. Preferably, theneedle 152 includes a needle manifold and a plurality of microneedles152.

The reservoir dome seal (flexible film) 164 of the reservoir subassembly120, as shown, for example, in FIG. 5, is disposed between the plunger144 and the dome 176. Reservoir contents (for example, medicinalmaterial) for the infusion device 100 are disposed in the space betweenthe reservoir dome seal 164 and the dome 176. The combination of thereservoir dome seal 164, the dome 176, and the space therebetweendefines a reservoir 160. The dome 176 is preferably transparent topermit viewing of the reservoir contents. The reservoir dome seal 164can be made of non-distensible materials or laminates, such asmetal-coated films or other similar substances. For example, onepossible flexible laminate film that can be used in the reservoir domeseal 164 includes a first polyethylene layer, a second chemical layer asknown to those skilled in the art to provide an attachment mechanism fora third metal layer which is chosen based upon barrier characteristics,and a fourth layer that includes polyester and/or nylon. By utilizing ametal-coated or metalized film in conjunction with a rigid portion (forexample, dome 176), the barrier properties of the reservoir 160 areimproved, thereby increasing or improving the shelf life of the contentscontained within. For example, where reservoir contents includesinsulin, the primary materials of contact in the reservoir 160 includelinear, low-density polyethylene (LLDPE), low-density polyethylene(LDPE), cyclic olefin copolymer (COC) and Teflon. As described ingreater detail below, the primary materials of contact in the remainingflow path of the reservoir contents may also include COC and LLDPE, aswell as thermoplastic elastomer (TPE), medical grade acrylic, stainlesssteel, and a needle adhesive (e.g. a UV cured adhesive). Such materialsthat remain in extended contact with the contents of the reservoir 160preferably pass ISO 10-993 and other applicable biocompatibilitytesting.

The reservoir subassembly 120 is further preferably able to be storedfor the prescribed shelf life of the reservoir contents in applicablecontrolled environments without adverse effect to the contents, and iscapable of applications in a variety of environmental conditions.Additionally, the barrier provided by the components of the reservoirsubassembly 120 do not permit the transport of gas, liquid, and/or solidmaterials into or out of the contents at a rate greater than thatallowable to meet the desired shelf life. In the embodiments shownabove, the reservoir materials are capable of being stored and operatedin a temperature range of approximately 34 to 120 degrees Fahrenheit andcan have a shelf life of two or more years.

In addition to satisfying stability requirements, the reservoirsubassembly 120 can further ensure operation by successfully passing anynumber of leak tests, such as holding a 30 psi sample for 20 minuteswithout leaking. Additional filling, storage and delivery benefitsresulting from the configuration of the reservoir include minimizedheadspace and adaptability as described in greater detail below.

In one embodiment, the reservoir 160 is evacuated prior to filling. Byevacuating the reservoir 160 prior to filling and having only a slightdepression in the dome 176, headspace and excess waste within thereservoir 160 can be minimized. In addition, the shape of the reservoircan be configured to adapt to the type of energizing mechanism (forexample, pressurization spring 140 and plunger 144) used. Additionally,using an evacuated flexible reservoir 160 during filling minimizes anyair or bubbles within the filled reservoir 160. The use of a flexiblereservoir 160 is also very beneficial when the infusion device 100 issubjected to external pressure or temperature variations, which can leadto increased internal reservoir pressures. In such case, the flexiblereservoir 160 expands and contracts with the reservoir contents, therebypreventing possible leaks due to expansion and contraction forces.

Yet another feature of the reservoir 160 includes the ability to permitautomated particulate inspection at the time of filling or by a patientat the time of use. One or more reservoir barriers, such as the dome176, can be molded of a transparent, clear plastic material, whichallows inspection of the substance contained within the reservoir. Thetransparent, clear plastic material is preferably a cyclic olefincopolymer that is characterized by high transparency and clarity, lowextractables, and biocompatibility with the substance contained in thereservoir 160. A suitable material is available from Zeon Chemicals,L.P., of Louisville, Ky. under the designation “BD CCP Resin,” and islisted by the U.S. Food and Drug Administration and DMF No. 16368. Insuch applications, the reservoir 160 includes minimal features thatcould possibly obstruct inspection (i.e. rotation during inspection ispermitted).

Channel arm 172 is provided in the form of at least one flexible arcuatearm extending from the valve 168 to the needle manifold or microneedles152. The arcuate arm has a groove 174 (see, for example, FIG. 2) formedtherein. To provide a fluid path between valve 168 and the needlemanifold or microneedles 152, the reservoir arm seal 180 covers thegroove 174. The fluid path (disposed in channel arm 172—shown, forexample, in FIG. 8) between the reservoir 160 and the microneedles 152is constructed of materials similar or identical to those describedabove for the reservoir 160. For example, channel arm 172 may beconstructed of the same material as the dome 160 and the reservoir armseal 180 may constructed of the same material as the reservoir dome seal164. According to one embodiment, both channel arms 172 are employed asfluid paths between the valve 168 and the needle manifold ormicroneedles 152. According to another embodiment, only one of thechannel arms 172 is employed as a fluid path, and the remaining channelarm 172 provides structural support. In such an embodiment, the groove174 extends fully from the valve 168 to the needle manifold ormicroneedles 152 only in the channel arm 174 that will be employed asthe fluid path.

The channel arm 172 must be sufficiently flexible to withstand the forceof activation. Contrasting the position of the channel arm 172 in FIGS.2 and 8, the channel arm 172 (covered by reservoir arm seal 180 in FIG.2, which is removed in FIG. 8 for clarity) elastically deforms when themicroneedles 152 are driven into the patient's skin (described ingreater detail below). During such deformation, the channel arm 172 mustmaintain the integrity of the fluid path between the valve 168 and theneedle manifold or microneedles 152. Additionally, the materials for thechannel arm 172 satisfy numerous biocompatibility and storage tests. Forexample, as shown in Table 1 below, where an infusion device contentincludes insulin, the primary materials of contact in the reservoir 160include linear, low-density polyethylene, cyclic olefin copolymer, andTeflon, and can also include a transparent, clear plastic. The primarymaterials of contact in the remaining flow path (channel 62) between thereservoir 160 and the microneedles 152 of the needle manifold includeCOC and/or medical grade acrylic, LLDPE, TPE, and stainless steel, aswell as the needle adhesive.

TABLE 1 Path Component Material Reservoir Polyethylene, cyclic olefincopolymer, and/or Teflon Reservoir Dome Seal Metal-coated film, such aspolyethylene, aluminum, polyester, and/or nylon with a chemical tielayer Valve TPE Needle Manifold COC and/or medical grade acrylic Needleadhesive UV-cured adhesive Microneedle Stainless steel

More specifically, the microneedles 152 can be constructed of stainlesssteel, and the needle manifold can be constructed of polyethylene and/ormedical grade acrylic. Such materials, when in extended contact with thecontents of the reservoir, preferably pass ISO 10-993 biocompatibilitytesting.

The valve 168, disposed between the reservoir 160 and the channel arm172, selectively permits and restricts fluid flow between the reservoir160 and the channel arm 172. The valve 168 moves between a pre-activatedposition (shown, for example, in FIGS. 2, 3, and 6) and an activatedposition (shown, for example, in FIGS. 8-10). When in the activatedposition, the valve permits fluid flow between the reservoir 160 and thechannel arm 172, and therefore to the needle manifold and microneedles152.

In use, the valve 168 will eventually be pushed into the activatedposition by the movement of the activator button 128, best illustratedby the movement of the valve 168 between FIGS. 5 and 10. As shown inFIG. 10, the movement of the valve 168 advances the enlarged distal endof the valve 168, thereby permitting the drug to flow from the reservoir160 into the channel arm 172 and down the fluid path to the needlemanifold.

The embodiment described above includes at least one needle 152, ormicroneedle 152, but may contain several, such as the two illustratedmicroneedles 152. Each microneedle 152 is preferably at least 31 gaugeor smaller, such as 34 gauge, and is anchored within a patient needlemanifold that can be placed in fluid communication with the reservoir160. The microneedles 152, when more than one is included in theinfusion device 100, can also be of differing lengths, or gauges, or acombination of both differing lengths and gauges, and can contain one ormore ports along a body length, preferably located near the tip of themicroneedle 152 or near the tip bevel if any of the microneedles 152 hasone.

According to one embodiment, the gauge of the microneedles 152 governsthe delivery rate of reservoir contents of the infusion device 100. Theuse of multiple 34 gauge microneedles 152 to deliver the reservoircontents is practical when the infusion occurs over a longer period thantypically associated with an immediate syringe injection requiring amuch larger cannula, or needle. In the disclosed embodiments, anymicroneedles 152 that target either an intradermal or subcutaneous spacecan be used, but the illustrated embodiments include intradermalmicroneedles 152 of between 1 and 7 mm in length (i.e., 4 mm). Thearrangement of the microneedles 152 can be in a linear or nonlineararray, and can include any number of microneedles 152 as required by thespecific application.

As noted above, the microneedles 152 are positioned in a needlemanifold. In the needle manifold, at least one fluid communication pathis provided to each microneedle 152. The manifold may simply have asingle path to one or more microneedles 152, or may provide multiplefluid paths or channels routing the reservoir contents to eachmicroneedle 152 separately. These paths or channels may further comprisea tortuous path for the contents to travel, thereby affecting fluidpressures and rates of delivery, and acting as a flow restrictor. Thechannels or paths within the needle manifold can range in width, depthand configuration depending upon application, where channel widths aretypically between about 0.015 and 0.04 inch, preferably 0.02 inch, andare constructed to minimize dead space within the manifold.

According to one embodiment, the reservoir subassembly 120 has a pair ofholes 184 and 188 to aid registration of the reservoir subassembly 120with respect to the bottom enclosure 104. First and second posts 192 and196 (described in greater detail below) of the bottom enclosure 104 areinserted through the respective holes 184 and 188.

In exploded views with the reservoir subassembly 120 removed, FIGS. 4,7, and 9 illustrate that bottom enclosure 104 includes a substantiallycylindrical housing 200 in which pressurization spring 140 and plunger144 are disposed. According to one embodiment, cylindrical housing 200includes a plurality of recessed channels 204 to guide a respectiveplurality of legs 208 and feet 212 of the plunger 144 as the plungertranslates within the housing 200. Collectively, a leg 208 and a foot212 constitute a plunger tab 214. As shown in FIGS. 4, 7, and 9, forexample, the recessed channels 204 extend only part of the way down thecylindrical housing 200 from a top thereof. Below the recessed channels204, there are openings 216 through which the feet 212 of plunger 144can extend outside of the cylindrical housing 200. The openings 216 aresubstantially L-shaped with horizontal portions at the base of thecylindrical housing 200, and a vertical portion substantially alignedwith the recessed channels 204.

When the infusion device 100 is in the pre-activated state, thepressurization spring 140 is compressed by the plunger 144 (as shown,for example, in FIGS. 4-6), and the feet 212 of the plunger 144 aresubstantially disposed in the horizontal portions of the openings 216.The force of the pressurization spring 140 biases the feet 212 of theplunger 144 against a top of the horizontal portions of the openings 216(i.e., a ledge of the cylindrical housing 200). Together, as describedin greater detail below, the pressurization spring 140 and the plunger144 form a pressurizing system to pressurize the reservoir 160 when theinfusion device 100 is activated.

As described in greater detail below, the rotor 136 rotates around thebase of the cylindrical housing 200 between a pre-activated position(illustrated, for example, in FIGS. 2-4) and an activated position(illustrated, for example, in FIGS. 8-10). When the rotor 136 rotatesfrom the pre-activated position to the activated position, at least onefoot engaging surface 220 (shown, for example, in FIG. 4) of the rotor136 engages at least one of the feet 212 of the plunger 144 and rotatesthe plunger 144 so that the feet 212 align with the vertical portions ofthe openings 216 and the recessed channels 204. At this point, thepressurization spring 140 moves the plunger 144 upward with the feet 212being guided by the raised channels 204.

The pressurization spring 140 is included in the infusion device 100 toapply an essentially even force to the reservoir 160, to force thecontents from the reservoir 160. The pressurization spring 140 is usedto store energy that, when released, pressurizes the reservoir 160 atthe time of use. The pressurization spring 140 is held in a compressedstate by engagement between feet 212 of the plunger 144 and thecylindrical housing 200. This engagement prevents the pressurizationspring 140 from putting stress on a film (to be described later) of thereservoir 160 or any remaining device components (other than the bottomenclosure 104 and the plunger 144 ) during storage. The plunger 144 issufficiently rigid to resist spring tension and deformation, and shouldnot fail under normal load.

As noted above, when the rotor 136 rotates from the pre-activatedposition to the activated position, the rotor 136 engages at least oneof the feet 212 of the plunger 144 and rotates the plunger 144 to alignthe feet 212 with the vertical portions of the openings 216 and therecessed channels 204. The compressed pressurization spring 140, thenmoves the plunger 144 upward, and in doing so, exerts a force on thefilm of the reservoir 160. The pressurization spring 140 can beconfigured to preferably create a pressure within the reservoir 116 offrom about 1 to 50 psi, and more preferably from about 2 to about 25 psifor intradermal delivery of the reservoir contents. For sub-cutaneousinjection or infusion, a range of about 2 to 5 psi may be sufficient.

According to one embodiment, the activator button 128 includes thepatient interface surface 132 that the patient presses to activate theinfusion device 100. The activator button 128 also includes a hinge arm224 and an activation arm 228 (both shown, for example, in FIGS. 3 and11A). The hinge arm 224 of the activator button 128 includes acylindrical portion with an opening (see, for example, FIG. 11A). Theactivation arm 228 includes a tab 230 (see for example, FIG. 3).According to one embodiment, the tab 230 includes a bearing surface 232and a locking surface 234 disposed adjacent to the cantilevered end ofthe bearing surface 232. According to one embodiment, the tab 230 formsan acute angle with a main portion of the activation arm 228.

The first post 192, disposed on the bottom enclosure 104, extendsupwardly therefrom. According to one embodiment (as shown, for example,in FIGS. 4 and 7), a base of the first post 192 includes a pair of flatsides 236 and a pair of rounded sides 240. Additionally, as shown, forexample, in FIGS. 4 and 7, the second post 196 and first and seconddrive spring bases 244 and 248 extend upwardly from the bottom enclosure104. As will be described in greater detail below, the first and seconddrive spring bases 244 and 248 anchor respective ends of drive spring148. The first drive spring base 244 is disposed adjacent to the secondpost 196 with a space therebetween.

According to one embodiment, FIGS. 3 and 6 illustrate the positioning ofthe activator button 128 with respect to the bottom enclosure 104, forassembly of the activator button 128. In this position, the opening ofthe cylindrical portion of the hinge arm 224 allows the activator button128 to slide horizontally (passing the flat sides 236) and engage thefirst post 192. The hinge arm 224 (and therefore the activator button128) can then rotate about the first post 192. As the activation arm 228passes into the space between the second post 196 and the first drivespring base 244, at least one of the tab 230 and the activation arm 228elastically deforms until a cantilevered end of the bearing surface 232of tab 230 passes a retaining face 252 of the second post 196. Thepassage of the cantilevered end of the bearing surface 232 of tab 230past the retaining face 252 (see, for example, FIG. 4) of the secondpost 196 and the engagement of the locking surface 234 of tab 230 withthe retaining face 252 provides an audible click and tactile feedbackconveying that the activator button 128 is in the pre-activatedposition.

FIGS. 11A and 11B illustrate embodiments of the activation arm 228 ofthe activator button 128. As shown in FIG. 11A, the activation arm 228includes a locking portion 256 disposed at an end thereof and a cutout260A extending a portion of a distance from the locking portion 256 to abase of the activation arm 228. In contrast, in the embodimentillustrated in FIG. 11B, the cutout 260B extends from the lockingportion 256 to the base of the activation arm. The locking portion 256includes a bearing surface 264 (best shown in FIG. 3) adjoining alocking surface 266. The locking surface 266 is disposed at a rear edgeof the locking portion 256.

Illustrated in FIG. 12 is an embodiment of the second post 196 of thebottom enclosure 104. The second post 196 includes a button guide latch268. The button guide latch 268 includes a guide surface 270 and aretaining surface 272. According to one embodiment, as shown in FIG. 12,the guide surface 270 and the retaining surface 272 adjoin at an end ofthe button guide latch 268 forming an acute angle (a) therebetween withrespect to the button guide latch 268.

FIGS. 13A and 13B illustrate interaction between the activation arm 228and the button guide latch 268 prior to and subsequent to activation ofthe infusion device 100. The rotor 136 and the tab 230 of the activationarm 228 are not shown in FIGS. 13A and 13B for clarity of illustration.As shown in FIG. 13A, the bearing surface 264 of the locking portion 256directly contacts and slides along the guide surface 270 of the buttonguide latch 268 as the patient moves the activator button 128 from thepre-activated position to the activated position. According to oneembodiment, the contact between the bearing surface 264 and the guidesurface 270 elastically deforms at least one of the bearing surface 264and the guide surface 270.

As the activator button 128 reaches the activated position, as shown inFIG. 13B, the end of the activation arm 228 engages with the buttonguide latch 268, and prevents return movement of the activator button128. More specifically, the cutout 260 (A or B) permits the activationarm 228 to pass over the end of the guide surface 270, thereby engagingthe locking portion 256 with the retaining surface 272 of the buttonguide latch 268. In greater detail, the bearing surface 264 directlycontacts and slides along the guide surface 270 until reaching the endof the button guide latch 268. At this point, the cutout 260 (A or B)aligns with the end of the button guide latch 268 and the elasticallydeformed surface (at least one of the bearing surface 264 and the guidesurface 270) returns to its substantially un-deformed state. Thus, theactivation arm, 228 passes over the end of the guide surface 270 due tothe presence of the cutout 260 (A or B), and the locking surface 266 ofthe activation arm 228 engages the retaining surface 272 of the buttonguide latch 268.

As shown in FIG. 13B, a side wall of the bottom enclosure 104substantially prevents further forward travel of the activation arm 228past the activated position. According to one embodiment, either insteadof, or in addition to the side wall of the bottom enclosure 104,restricted travel of the rotor 136 and the engagement between the rotor136 and the activation arm 228 substantially prevents further forwardtravel of the activation arm 228 past the activated position.

Additionally, though the rotor 136 is not shown in FIGS. 13A and 13B,FIGS. 13A and 13B illustrate the motion of the plunger 144 with respectto the cylindrical housing 200 as the activator button 128 and the rotor136 move from the pre-activated position to the activated position. InFIG. 13A, the plunger tabs 214 remain engaged with the horizontalportions of the L-shaped openings 216 of the cylindrical housing 200. InFIG. 13B, however, in which the activator button 128 and the rotor 136have reached the activated position, the plunger 144 has been rotated sothat the plunger tabs 214 align with the vertical portion of theL-shaped openings 216 (and the recessed channels 204), therebypermitting the plunger 144 to translate within the cylindrical housing200 due to the force of the pressurization spring 140.

FIGS. 14A and 14B illustrate another embodiment of a button guide latch268A prior to and subsequent to activation of the infusion device 100.More specifically, FIG. 14A, illustrates the activator button 128 in thepre-activated position, in which the locking surface 234 of the tab 230engages the retaining face 252 of the second post 196. As shown in FIG.14A, the button guide latch 268A includes a retaining post 274 extendingsubstantially perpendicular from the top surface of the bottom enclosure104. The retaining post 274 includes a guide surface 270A and aretaining surface 272A disposed adjacent to the guide surface 270A at anend thereof. When the activator button 128 moves from the pre-activatedposition to the activated position (shown, for example, in FIG. 14B),the bearing surface 232 directly contacts and slides along the guidesurface 270A until the cantilevered end of the bearing surface 232passes the end of the guide surface 270A. Then, the locking surface 234of the tab 230 engages the retaining surface 272A of the retaining post274 (shown in FIG. 14B).

As the activator button 128 moves from the pre-activated position to theactivated position, the contact between the bearing surface 232 and theguide surface 270A elastically deforms at least one of the bearingsurface 232, the guide surface 270A, and the activation arm 228 until acantilevered end of the bearing surface 232 of tab 230 passes the guidesurface 270A of the retaining post 274. At this point, the at least onedeformed surface/activator arm returns to a substantially un-deformedstate. The passage of the cantilevered end of the bearing surface 232 oftab 230 past the guide surface 270A and the engagement of the lockingsurface 234 of tab 230 with the retaining surface 272A provides anaudible click and tactile feedback conveying that the activator button128 is in the activated position.

Additionally, as shown most clearly in FIG. 14B, bottom enclosure 104includes first and second lock-defeating holes 276 and 278 respectivelydisposed adjacent to the second post 196 and the retaining post 274. Ifnecessary, a device (for example, a paper clip) can be inserted throughthe first or second lock-defeating holes 276 and 278, to press againstthe bearing surface 232 of tab 230 to disengage the locking surface 234of tab 230 from the retaining face 252 of second post 196 or theretaining surface 272A of retaining post 274. According to oneembodiment, at least second lock-defeating hole 278 is covered by anadhesive pad (described in greater detail below).

Thus, the locking mechanisms for the activator button 128 hold theactivator button 128 in place after activation of the infusion device100. Accordingly, with such locking mechanisms, a patient can quicklyand easily determine whether the infusion device 100 has been activated.Also, the activator button 128 will not will not move freely back andforth (or rattle) subsequent to activation.

Referring back to FIGS. 2-4, and 7-9, rotor 136 additionally includes anactivation projection 284 and a drive spring holder 288. The activationarm 228 of the activator button 128 engages the activation projection284 when a patient depresses the activator button 128, thereby rotatingthe rotor 136 from the pre-activated position to the activated position.

The drive spring holder 288 maintains the drive spring 148 in apre-activated position when the rotor 136 is in the pre-activatedposition. As noted previously, the first and second drive spring bases244 and 248 anchor opposing ends of the drive spring 148. Atapproximately a midpoint of the drive spring 148, there is asubstantially U-shaped projection as shown, for example, in FIGS. 2 and3, for engagement with the drive spring holder 288 of the rotor 136.Accordingly, when the rotor 136 is in the pre-activated position and thedrive spring 148 engages the drive spring holder 288, the drive spring148 is maintained in a tensile state. And when the drive spring holder288 releases the drive spring 148 (i.e., when the rotor rotates from thepre-activated position to the activated position as illustrated, forexample, in FIGS. 8-10), the drive spring 148 drives the microneedles152 to extend outside of the infusion device 100 through an opening 328in the bottom enclosure 104 (and through an opening in the safetymechanism 108 described in greater detail below).

Thus, as will be described in greater detail below, the activation andenergizing of the infusion device 100 that is accomplished in a singlemulti-function/step process includes depression of the activator button128 by a patient, and rotation of the rotor 136 due to engagementbetween the activation arm 228 of the activator button 128 and theactivation projection 284 of the rotor 136. As described above, therotation of the rotor 136 rotates and releases the plunger 144 topressurize the fluid within the reservoir 160. Additionally, therotation of the rotor 136 releases the drive spring 148 from the drivespring holder 288, thereby driving the microneedles 152 to extendoutside of the infusion device 100. The single multi-function/stepprocess also includes movement of the valve 168 from the pre-activatedposition to the activated position due to the activator button 128engaging and moving the valve 168 when the activator button 128 isdepressed, thereby commencing fluid flow between the reservoir and themicroneedles 152 via the channel arm 172.

As noted above, the patch-like infusion device 100 also includes asafety mechanism 108. To prevent inadvertent or accidental needle stickinjuries, prevent intentional re-use of the device, and to shieldexposed needles, the locking needle safety mechanism 108 is provided.The safety mechanism 108 automatically activates immediately uponremoval of the infusion device 100 from the skin surface of the patient.According to one embodiment described in greater detail below, aflexible adhesive pad 292 adheres to a bottom portion of the bottomenclosure 104 and a bottom portion of the safety mechanism 108. Theadhesive pad 292 contacts with the patient's skin and holds the infusiondevice 100 in position on the skin surface during use. As shown, forexample, in FIGS. 15 and 16, upon removal of the infusion device 100from the skin surface, the safety mechanism 108 extends to a positionshielding the microneedles 152. When fully extended, safety mechanism108 locks into place and prevents accidental injury or exposure to thepatient needles 152.

In general, a passive safety system is most desirable. This allows thedevice to be self-protecting in case of accidental removal or if thepatient forgets that there is a safety step. Because one typical use forthis infusion device 100 is to provide human growth hormone, which isusually given in the evening, it can be expected that patients that wearthe device (such as children) may actually wear them overnight, eventhough the delivery may be expected to take less than 10 minutes.Without a passive system, if the infusion device 100 falls off, themicroneedles 152 could re-stick the patient or a caregiver. The solutionis to either limit the activities during use, or include a passivesafety system.

With respect to safety systems, there are typically three options. Afirst option is to retract the needles 152 into the device. A secondoption is to shield the needles 152 to remove access, and a third optionis to destroy the needles 152 in a way that prevents needle stickinjuries. Other systems, such as active systems, utilize manualshielding and/or destruction, or manual release of safety features withan additional button push or similar action. A detailed description ofpassive safety embodiments of the present invention is provided below.

One safety embodiment of the present invention is a passive, fullyenclosed pull-out design embodiment, such as safety mechanism 108. FIGS.5, 10, and 16 are perspective cutaway views of the infusion device 100that illustrate the safety mechanism 108 prior to activation, subsequentto activation, and subsequent to deployment of the safety mechanism 108,respectively.

When the infusion device 100 is removed from the skin, the flexibleadhesive pad 292 (attached to both the bottom surface of the bottomenclosure 104 and the bottom surface of the safety mechanism 108) willpull the safety mechanism 108 out and lock it into place before theadhesive pad 292 releases the skin surface. In other words, the forcerequired to remove the adhesive pad from the skin surface is greaterthan that required to deploy the safety mechanism 108. According to oneembodiment, the safety mechanism 108, as shown, for example, in FIG. 17,includes a flat surface portion 296 that is in contact with thepatient's skin. The flat surface portion 296 is where a portion ofadhesive pad 292 (shown as a dotted line in FIG. 17) is affixed tosafety mechanism 108 such that when the infusion device 100 is removedby the patient from the skin, the adhesive pad 292 will act to deploythe safety mechanism 108 from the infusion device 100, thereby shieldingthe microneedles 152, which otherwise would be exposed upon removal ofthe infusion device 100 from the patient. When the safety mechanism 108is fully extended, the safety mechanism 108 locks into place andprevents accidental injury or exposure to the microneedles 152.

According to one embodiment, the adhesive pad 292 is provided insubstantially two parts, one on the bulk of the bottom surface of thebottom enclosure 104, and one on the bottom surface of the safetymechanism 108. When the infusion device 100 is removed, the two patchesmove independently and the safety mechanism 108 is rotatable withrespect to the bottom enclosure 104. According to another embodiment,the two parts are formed as a unitary, flexible adhesive pad 292 withone part being disposed on the on the bulk of the bottom surface of thebottom enclosure 104, and one part disposed on the bottom surface of thesafety mechanism 108.

According to one embodiment, the safety mechanism 108 is a stamped metalpart. According to another embodiment, the safety mechanism 108 is madeof substantially the same material as the bottom enclosure 104. As shownin FIG. 18, the safety mechanism 108 includes a front shield 300, a pairof insertion tabs 304 disposed at a rear portion of the safety mechanism108, a pair of pivot tabs 308 disposed, respectively, at upper rear endsof a rim portion 312 of the safety mechanism 108, a guide post 316extending upwardly from a substantially flat bottom inner surface of thesafety mechanism 108, and locking posts 320 also extending upwardly fromthe bottom inner surface of the safety mechanism 108. Front shield 300extends above the rim portion 312 to shield the patient from themicroneedles 152 when the safety mechanism 108 is deployed. The guidepost 316 includes a cutout therein to engage a safety retainingprojection 324 of the rotor 136 (shown, for example, in FIGS. 7 and 9)when the rotor 136 is in the pre-activated position, to prevent thesafety mechanism 108 from deploying prior to activation of the infusiondevice 100.

Additionally, as noted above, the safety mechanism 108 includes theneedle opening 156. Prior to deployment of the safety mechanism 108, theneedle opening 156 at least partially overlaps the opening 328 in bottomenclosure 104 to provide space for movement of the microneedles 152. Thelocking posts 320 are respectively disposed adjacent to front side edgesof the needle opening 156. The bottom enclosure 104 includes a guidepostopening 332 (shown, for example, in FIGS. 7 and 9), a pair of insertiontab openings 336 (one of which is shown, for example, in FIG. 4)disposed adjacent to opposing side edges of the bottom enclosure 104,and a pair of pivot rests 340 disposed on opposing sides of the bottomenclosure 104 (shown, for example, in FIGS. 7 and 9).

Referring again to FIG. 18, insertion tabs 304 each include a connectingportion 344 and an extending portion 348. According to one embodiment,the connecting portions 344 extend from the bottom inner surface of thesafety mechanism 108 toward a rear of the infusion device 100 at anon-perpendicular angle with respect to the bottom inner surface of thesafety mechanism 108. Extending portions 348 each extend substantiallyperpendicularly from the extending portions 348 toward respective outersides of the safety mechanism 108. To assemble the safety mechanism 108to the bottom enclosure 104, safety mechanism 108 is held at anapproximately 45° angle with respect to the bottom enclosure 104 and theinsertion tabs 304 are inserted through the insertion tab openings 336.The safety mechanism 108 is then rotated to a position such that theguidepost 316 is inserted through the guidepost opening 332 and thebottom inner surface of the safety mechanism 108 is substantiallyparallel and in contact with the bottom surface of the bottom enclosure104.

Referring again to FIGS. 7 and 9, although these views illustrate therotor 136 in the activated position, the exploded nature of FIGS. 7 and9 is convenient to illustrate this stage of the assembly of the safetymechanism 108 to the bottom enclosure 104. It will be understood,however, that the safety mechanism 108 should be assembled to the bottomenclosure prior to activation. Subsequent to the upward rotation of thesafety mechanism 108, as shown in FIG. 4, safety mechanism 108translates rearward with respect to the bottom enclosure 104 such thatpivot tabs 308 clear respective front edges of the pivot rests 340 andare disposed above the pivot rests 340, the locking posts 320 aredisposed adjacent to side edges of the opening 328 of the bottomenclosure 104, and the safety retaining projection 324 of the rotor 136engages the guide post 316.

Returning to FIG. 18, each of the locking posts 320 includes a postextending portion 352 extending substantially perpendicular from theflat bottom inner surface of the safety mechanism 108, and a wedgeportion 356 disposed at an end of the post extending portion 352. As aheight of the wedge portion 356 increases with respect to the bottominner surface of the safety mechanism 108, a width of the wedge portion356 increases.

As the safety mechanism 108 deploys and rotates downward with respect tothe bottom enclosure 104, the wedge portions 356 act against respectiveside edges of the openings 180 of the bottom enclosure 104, causing thelocking posts 192 to deform elastically toward one another. As thesafety mechanism 108 is fully deployed, the tabs 308 become seated inpivot rests 340. Additionally, top edges of the wedge portions 356 passbottom edges of the opening 328 and the locking posts 320 snap back totheir substantially un-deformed states, providing an audible click andtactile feedback communicating that the safety mechanism 108 is fullydeployed, and therefore, that the microneedles 152 are covered.Returning to FIGS. 15 and 16, once the safety mechanism 108 is fullydeployed and the locking posts 320 have snapped back to theirsubstantially un-deformed states, the top edges of the wedge portions356 engage the bottom surface of the bottom enclosure 104 adjacent tothe opening 328, thereby preventing the safety mechanism 108 fromrotating upward with respect to the bottom enclosure 104 and exposingthe microneedles 152. Additionally, as noted above, front shield 300shields the patient from the microneedles 152.

Accordingly, the safety mechanism 108 is a passive safety embodimentprovided as a single part and provides a good lock that will not crushunder human loads. With this passive safety mechanism, no additionalforces are applied to the skin during injection, and the microneedles152 are safely held within the infusion device 100 after use.

After use of the infusion device 100, the patient can once again inspectthe device to ensure the entire dose was delivered. In this regard, asshown in FIGS. 19A-19D, the infusion device 100 includes the end-of-doseindicator (EDI) 124. The EDI 124 includes a main body 360 and first andsecond arms 364 and 340 extending substantially horizontally withrespect to a top of the main body 360.

The EDI 124 also includes a spring arm 372 that curves upwardly from thetop of the main body 360. According to one embodiment, the spring arm372 pushes against a bottom side of the reservoir subassembly 120,elastically biasing the EDI 124 toward the bottom enclosure 104, toensure that the EDI 124 does not move freely out of the infusion device100, for example, during shipping and handling of the infusion device100.

Returning to FIG. 4, the main body 360 is disposed in an EDI channel 376and translates substantially vertically therein. The EDI channeladjacent to one of the recessed channels 204 that guides legs 208 andfeet 212 of plunger 144. The first arm 364 extends across a top of thisrecessed channel 204.

Returning to FIG. 19A, a vertical extrusion 380 extends upwardly from anend of the second arm 368. When the reservoir contents have beendelivered, the vertical extrusion extends through an EDI opening 384(see, for example, FIG. 19C) in the top enclosure 116 to communicatethat the end of the dose has been reached. According to one embodiment,the EDI 124 is formed as a one-piece construction.

As shown in FIG. 19B, as the plunger 144 travels upwardly in thecylindrical housing 200 due to the pressurization spring 140 subsequentto activation, one of the feet 212 of the plunger 144 contacts the firstarm of the EDI 124. The foot 212 lifts the EDI 124 upward, overcomingthe bias of the spring arm 372, and causing the vertical extrusion 380to increasingly extend through the EDI opening 384 during delivery ofthe reservoir contents. Referring back to FIG. 10, vertical extrusion380 partially extends from the infusion device 100. Once the delivery ofthe reservoir contents is complete and the plunger has achieved its fullstroke, the vertical extrusion 380 is fully extended, as shown in FIG.19D. Thus, the EDI 124 employs the linear movement of the plunger 144 togenerate linear movement of the EDI 124 that is visible outside of theinfusion device 100 thereby communicating the delivery of the reservoircontents.

FIG. 20 illustrates an embodiment of an infusion device 700 with aninjection port 704. The injection port provides access to a reservoir708, whether evacuated or partially filled, so that the patient caninject a substance or combination of substances into the reservoir priorto activation. Alternatively, a pharmaceutical manufacturer orpharmacist could employ the injection port 704 to fill the infusiondevice 700 with a substance or combination of substances prior to sale.In substantially all other respects, the infusion device 700 is similarto the previously-described infusion device 100.

Operation of the infusion device 100 will now be described. Theembodiments of the present invention described above preferably includea push-button (activator button 128) design wherein the infusion device100 can be positioned and affixed to a skin surface, and energizedand/or activated by pressing the activator button 128. Morespecifically, in a first step, the patient removes the device from asterile packaging (not shown), removes a cover (not shown) of theadhesive pad 292. The patient also removes the needle cover 112. Uponremoval of the infusion device 100 from the package and prior to use(see, for example, FIGS. 1, 2, 4, and 5), the infusion device 100 in thepre-activated state allows the patient to inspect both the device andthe contents therein, including inspection for missing or damagedcomponents, expiration dates(s), hazy or color-shifted drugs, and soforth.

The next step is the positioning and application of the infusion device100 to the patient's skin surface. Like a medicinal patch, the patientfirmly presses the infusion device 100 onto the skin. One side of theadhesive pad 292 adheres to a bottom surface of the bottom enclosure 104and a bottom surface of the safety mechanism 108, and the opposing sideof the adhesive pad 292 secures the infusion device 100 to the skin ofthe patient. These bottom surfaces (of the bottom enclosure 104 and thesafety mechanism 108) can be flat, contoured, or shaped in any suitablefashion and the adhesive pad 292 is secured thereon. According to oneembodiment, prior to shipping, the cover of the adhesive pad 292, suchas a film, is applied to the patient-side of the adhesive pad 292 topreserve the adhesive during shipping. As noted above, prior to use, thepatient peels back the adhesive cover, thereby exposing the adhesive pad292 for placement against the skin.

After removing the adhesive cover, the patient is able to place theinfusion device 100 against the skin and press to ensure properadhesion. As noted above, once properly positioned, the device isactivated by depressing the activator button 128. This activation stepreleases plunger 144 and the pressurization spring 140, allowing aplunger 144 to press against the flexible film (reservoir dome seal 164)of the reservoir 160, thereby pressurizing the reservoir. Thisactivation step also serves to release the drive spring 148 from thedrive spring holder 288 of the rotor 136, thereby driving themicroneedles 152 to extend outside the infusion device 100 (through theopening 328 in the bottom enclosure 104 and the needle opening 156 ofthe safety mechanism 108) and seat the microneedles 152 within thepatient. Further, the activation step opens the valve 168, establishinga fluid communication path between the reservoir 160 and themicroneedles 152, via the channel arm 172 (see, for example, FIGS.8-10). A significant benefit derives from the ability to achieve each ofthese actions in a single push-button operation. Additionally, anothersignificant benefit includes the use of a continuous fluid communicationpath comprised entirely within the reservoir subassembly 120.

Once activated, the patient typically leaves the infusion device 100 inposition, or wears the device, for some period of time (such as tenminutes to seventy-two hours) for complete delivery of the reservoircontents. The patient then removes and discards the device with nodamage to the underlying skin or tissue. Upon intentional or accidentalremoval, one or more safety features deploy to shield the exposedmicroneedles 152. More specifically, when the infusion device 100 isremoved by the patient from the skin, the adhesive pad 292 acts todeploy the safety mechanism 108 from the infusion device 100, therebyshielding the microneedles 152, which otherwise would be exposed uponremoval of the infusion device 100 from the patient. When the safetymechanism 108 is fully extended, the safety mechanism 108 locks intoplace and prevents accidental injury or exposure to the microneedles152. The safety features, however, can be configured to not deploy ifthe activator button 128 has not been depressed and the microneedles 152have not been extended, thereby preventing pre-use safety mechanismdeployment. After use, the patient can once again inspect the device toensure the entire dose was delivered. For example, the patient can viewthe reservoir interior through the transparent dome 176 and/or inspectthe EDI 124.

The described embodiments are suitable for use in administering varioussubstances, including medications and pharmaceutical agents, to apatient, and particularly to a human patient. As used herein, apharmaceutical agent includes a substance having biological activitythat can be delivered through the body membranes and surfaces, andparticularly the skin. Examples, listed in greater detail below, includeantibiotics, antiviral agents, analgesics, anesthetics, anorexics,antiarthritics, antidepressants, antihistamines, anti-inflammatoryagents, antineoplastic agents, vaccines, including DNA vaccines, and thelike. Other substances that can be delivered intradermally orsubcutaneously to a patient include human growth hormone, insulin,proteins, peptides and fragments thereof. The proteins and peptides canbe naturally occurring, synthesized or recombinantly produced.Additionally, the device can be used in cell therapy, as duringintradermal infusion of dendritic cells. Still other substances whichcan be delivered in accordance with the method of the present inventioncan be selected from the group consisting of drugs, vaccines and thelike used in the prevention, diagnosis, alleviation, treatment, or cureof disease, with the drugs including Alpha-1 anti-trypsin,Anti-Angiogenesis agents, Antisense, butorphanol, Calcitonin andanalogs, Ceredase, COX-II inhibitors, dermatological agents,dihydroergotamine, Dopamine agonists and antagonists, Enkephalins andother opioid peptides, Epidermal growth factors, Erythropoietin andanalogs, Follicle stimulating hormone, G-CSF, Glucagon, GM-CSF,granisetron, Growth hormone and analogs (including growth hormonereleasing hormone), Growth hormone antagonists, Hirudin and Hirudinanalogs such as hirulog, IgE suppressors, Insulin, insulinotropin andanalogs, Insulin-like growth factors, Interferons, Interleukins,Leutenizing hormone, Leutenizing hormone releasing hormone and analogs,Low molecular weight heparin, M-CSF, metoclopramide, Midazolam,Monoclonal antibodies, Narcotic analgesics, nicotine, Non-steroidanti-inflammatory agents, Oligosaccharides, ondansetron, Parathyroidhormone and analogs, Parathyroid hormone antagonists, Prostaglandinantagonists, Prostaglandins, Recombinant soluble receptors, scopolamine,Serotonin agonists and antagonists, Sildenafil, Terbutaline,Thrombolytics, Tissue plasminogen activators, TNF—, and TNF—antagonist,the vaccines, with or without carriers/adjuvants, includingprophylactics and therapeutic antigens (including but not limited tosubunit protein, peptide and polysaccharide, polysaccharide conjugates,toxoids, genetic based vaccines, live attenuated, reassortant,inactivated, whole cells, viral and bacterial vectors) in connectionwith, addiction, arthritis, cholera, cocaine addiction, diphtheria,tetanus, HIB, Lyme disease, meningococcus, measles, mumps, rubella,varicella, yellow fever, Respiratory syncytial virus, tick bornejapanese encephalitis, pneumococcus, streptococcus, typhoid, influenza,hepatitis, including hepatitis A, B, C and E, otitis media, rabies,polio, HIV, parainfluenza, rotavirus, Epstein Barr Virus, CMV,chlamydia, non-typeable haemophilus, moraxella catarrhalis, humanpapilloma virus, tuberculosis including BCG gonorrhoea, asthma,atheroschlerosis malaria, E-coli, Alzheimers, H. Pylori, salmonella,diabetes, cancer, herpes simplex, human papilloma and the like othersubstances including all of the major therapeutics such as agents forthe common cold, Anti-addiction, anti-allergy, anti-emetics,anti-obesity, antiosteoporeteic, anti-infectives, analgesics,anesthetics, anorexics, antiarthritics, antiasthmatic agents,anticonvulsants, anti-depressants, antidiabetic agents, antihistamines,anti-inflammatory agents, antimigraine preparations, antimotion sicknesspreparations, antinauseants, antineoplastics, antiparkinsonism drugs,antipruritics, antipsychotics, antipyretics, anticholinergics,benzodiazepine antagonists, vasodilators, including general, coronary,peripheral and cerebral, bone stimulating agents, central nervous systemstimulants, hormones, hypnotics, immunosuppressives, muscle relaxants,parasympatholytics, parasympathomimetrics, prostaglandins, proteins,peptides, polypeptides and other macromolecules, psychostimulants,sedatives, sexual hypofunction and tranquilizers and major diagnosticssuch as tuberculin and other hypersensitivity agents as described inU.S. Pat. No. 6,569,143, entitled “Method of Intradermally InjectingSubstances”, the entire content of which is expressly incorporatedherein by reference.

Vaccine formulations which can be delivered in accordance with thesystem and method of the present invention can be selected from thegroup consisting of an antigen or antigenic composition capable ofeliciting an immune response against a human pathogen, which antigen orantigenic composition is derived from HIV-1, (such as tat, nef, gp120 orgp160), human herpes viruses (HSV), such as gD or derivatives thereof orImmediate Early protein such as ICP27 from HSVI or HSV2, cytomegalovirus(CMV (esp Human) (such as gB or derivatives thereof), Rotavirus(including live-attenuated viruses), Epstein Barr virus (such as gp350or derivatives thereof), Varicella Zoster Virus (VZV, such as gpl, IIand IE63) or from a hepatitis virus such as hepatitis B virus (forexample Hepatitis B Surface antigen or a derivative thereof), hepatitisA virus (HAV), hepatitis C virus and hepatitis E virus, or from otherviral pathogens, such as paramyxoviruses: Respiratory Syncytial virus(RSV, such as F and G proteins or derivatives thereof), parainfluenzavirus, measles virus, mumps virus, human papilloma viruses (HPV forexample HPV6, 11, 16, 18), flaviviruses (e. g. Yellow Fever Virus,Dengue Virus, Tick-borne encephalitis virus, Japanese EncephalitisVirus) or Influenza virus (whole live or inactivated virus, splitinfluenza virus, grown in eggs or MDCK cells, or whole flu virosomes orpurified or recombinant proteins thereof, such as HA, NP, NA, or Mproteins, or combinations thereof), or derived from bacterial pathogenssuch as Neisseria spp, including N. gonorrhea and N. meningitidis (forexample capsular polysaccharides and conjugates thereof,transferrin-binding proteins, lactoferrin binding proteins, Pi1C,adhesins); S. pyogenes (for example M proteins or fragments thereof, C5Aprotease, lipoteichoic acids), S. agalactiae, S. mutans; H. ducreyi;Moraxella spp, including M catarrhalis, also known as Branhamellacatarrhalis (for example high and low molecular weight adhesins andinvasins); Bordetella spp, including B. pertussis (for examplepertactin, pertussis toxin or derivatives thereof, filamenteoushemagglutinin, adenylate cyclase, fimbriae),B. parapertussis and B.bronchiseptica; Mycobacterium spp., including M. tuberculosis (forexample ESAT6, Antigen 85A, -B or-C), M. bovis, M. leprae, M. avium, M.paratuberculosis M. smegmatis; Legionella spp, including L. pneumophila;Escherichia spp, including enterotoxic E. coli (for example colonizationfactors, heat-labile toxin or derivatives thereof, heat-stable toxin orderivatives thereof), enterohemorragic E. coli, enteropathogenic E. coli(for example shiga toxin-like toxin or derivatives thereof); Vibrio spp,including V. cholera (for example cholera toxin or derivatives thereof);Shigella spp, including S. sonnei, S. dysenteriae, S. flexnerii;Yersinia spp, including Y. enterocolitica (for example a Yop protein),Y. pestis, Y. pseudotuberculosis; Campylobacter spp, including C. jejuni(for example toxins, adhesins and invasins) and C. coli; Salmonella spp,including S. typhi, S. paratyphi, S. choleraesuis, S. enteritidis;Listeria spp., including L. monocytogenes; Helicobacter spp, includingH. pylori (for example urease, catalase, vacuolating toxin); Pseudomonasspp, including P. aeruginosa; Staphylococcus spp., including S. aureus,S. Epidermidis; Enterococcus spp., including E. faecalis, E. faecium;Clostridium spp., including C. tetani (for example tetanus toxin andderivative thereof), C. botulinum (for example Botulinum toxin andderivative thereof), C. difficile (for example clostridium toxins A or Band derivatives thereof); Bacillus spp., including B. anthracis (forexample botulinum toxin and derivatives thereof); Corynebacterium spp.,including C. diphtheriae (for example diphtheria toxin and derivativesthereof); Borrelia spp., including B. Burgdorferi (for example OspA,OspC, DbpA, DbpB), B. garinii (for example OspA, OspC, DbpA, DbpB), B.afzelii (for example OspA, OspC, DbpA, DbpB), B. andersonii (for exampleOspA, OspC, DbpA, DbpB), B. Hermsii; Ehrlichia spp., including E. equiand the agent of the Human Granulocytic Ehrlichiosis; Rickettsia spp,including R. rickettsii; Chlamydia spp., including C. Trachomatis (forexample MOMP, heparin-binding proteins), C. pneumoniae (for exampleMOMP, heparin-binding proteins), C. psittaci; Leptospira spp., includingL . interrogans; Treponema spp., including T. pallidum (for example therare outer membrane proteins), T. denticola, T. hyodysenteriae; orderived from parasites such as Plasmodium spp., including P. Falciparum;Toxoplasma spp., including T. gondii (for example SAG2, SAG3, Tg34);Entamoeba spp., including E. histolytica; Babesia spp., including B.microti; Trypanosoma spp., including T. cruzi; Giardia spp., including Glamblia; Leshmania spp., including L. major; Pneumocystis spp.,including P. Carinii; Trichomonas spp., including T. vaginalis;Schisostoma spp., including S. mansoni, or derived from yeast such asCandida spp., including C. albicans; Cryptococcus spp., including C.neoformans, as described in PCT Patent Publication No. WO 02/083214,entitled “Vaccine Delivery System”, the entire content of which isexpressly incorporated herein by reference.

These also include other preferred specific antigens for M.tuberculosis, for example Tb Ra12, Tb H9, Tb Ra35, Tb38-1, Erd 14, DPV,MTI, MSL, mTTC2 and hTCC1. Proteins for M. tuberculosis also includefusion proteins and variants thereof where at least two, preferablythree polypeptides of M. tuberculosis are fused into a larger protein.Preferred fusions include Ra12-TbH9-Ra35, Erd14-DPV-MTI, DPV-MTI-MSL,Erd14-DPV-MTI-MSL-mTCC2, Erd14-DPV-MTI-MSL, DPV-MTI-MSL-mTCC2,TbH9-DPV-MTI. Most preferred antigens for Chlamydia include for examplethe High Molecular Weight Protein (HWMP), ORF3, and putative membraneproteins (Pmps). Preferred bacterial vaccines comprise antigens derivedfrom Streptococcus spp, including S. pneumoniae (for example capsularpolysaccharides and conjugates thereof, PsaA, PspA, streptolysin,choline-binding proteins) and the protein antigen Pneumolysin (BiochemBiophys Acta, 1989, 67, 1007; Rubins et al., Microbial Pathogenesis, 25,337-342), and mutant detoxified derivatives thereof. Other preferredbacterial vaccines comprise antigens derived from Haemophilus spp.,including H. influenzae type B (“Hib”, for example PRP and conjugatesthereof), non typeable H. influenzae, for example OMP26, high molecularweight adhesins, P5, P6, protein D and lipoprotein D, and fimbrin andfimbrin derived peptides or multiple copy variants or fusion proteinsthereof. Derivatives of Hepatitis B Surface antigen are well known inthe art and include, inter alia, PreS1, PreS2 S antigens. In onepreferred aspect the vaccine formulation of the invention comprises theHIV-1 antigen, gp120, especially when expressed in CHO cells. In afurther embodiment, the vaccine formulation of the invention comprisesgD2t as hereinabove defined.

In addition to the delivery of substances listed above, the infusiondevice 100 can also be used for withdrawing a substance from a patient,or monitoring a level of a substance in the patient. Examples ofsubstances that can be monitored or withdrawn include blood,interstitial fluid or plasma. The withdrawn substances can then beanalyzed for analytes, glucose, drugs, and the like.

Although only a few exemplary embodiments of the present invention havebeen described in detail above, those skilled in the art will readilyappreciate that many modifications are possible in the exemplaryembodiments without materially departing from the novel teachings andadvantages of this invention. Accordingly, all such modifications areintended to be included within the scope of the appended claims andequivalents thereof.

What is claimed is:
 1. A drug delivery device comprising: a bodyincluding a top enclosure and a bottom enclosure, the bottom enclosurehaving a surface including a button guide latch; a reservoir disposedwithin the body for containing a medicament; an injection needle forpenetrating the skin of the patient, the needle having a lumen andcommunicating with the reservoir when the device is activated; apressurizing system for pressurizing the reservoir when the device isactivated; and an activator button movably disposed on the body andmovable from a pre-activated position to an activated position, theactivator button including an activation arm; wherein when the activatorbutton is moved from the pre-activated position to the activatedposition, an end of the activation arm engages with the button guidelatch and prevents movement of the activator button from the activatedposition to the pre-activated position; wherein the button guide latchcomprises a retaining post; and wherein the end of the activation armcomprises a cantilevered tab extending from the activation arm.
 2. Thedevice according to claim 1, wherein: the retaining post comprises aguide surface and a retaining surface disposed adjacent to the guidesurface at an end of the guide surface; the tab comprises a bearingsurface and a locking surface disposed adjacent to a cantilevered end ofthe bearing surface; and when the activator button is moved from thepre-activated position to the activated position, the bearing surfacedirectly contacts and slides along the guide surface until thecantilevered end of the bearing surface passes the end of the guidesurface and the locking surface of the tab engages the retaining surfaceof the retaining post.
 3. The device according to claim 2, wherein: whenthe activator button is moved from the pre-activated position to theactivated position, the contact between the bearing surface and theguide surface deforms at least one of the bearing surface, the guidesurface, and the activation arm; and the at least one deformed surfacereturns to a substantially un-deformed state when the cantilevered endof the bearing surface passes the end of the guide surface.
 4. Thedevice according to claim 1, wherein the tab forms an acute angle with amain portion of the activation arm.
 5. The device according to claim 1,wherein the retaining post extends substantially perpendicular from thesurface of the bottom enclosure.